Overall, localized delivery of therapeutics offer the possibility of increased drug effectiveness while minimizing side effects often associated with systemic drug administration. Factors that affect the possibility of targeting therapeutics to reach the vascular wall include the ability to 1) identify disease-specific target epitope expressed by the vascular cells; 2) identify optimum drug carrier type, shape and size for efficient interaction with the vascular wall; and 3) identify a drug-carrier combination that allow for the effective release of therapeutics at the intended site. Existing literature have focused mainly on identifying target epitopes and the degradation/drug release characteristics of a wide range of drug-carrier formulations. Absent in the literature, are work focused on the potential roles of particle shape and size on the ability of vascular-targeted drug carriers to interact with the vessels – an important consideration that will control the effectiveness of drug targeting regardless of the targeted disease or delivered therapeutic. Submicron to nanometer-sized spherical particles are widely proposed for use in vascular drug delivery, yet very little evidence has been presented in the literature as to their optimal use for vascular-targeted drug delivery. This talk will discuss how particle size and shape along with blood flow dynamics, vessel size and hematocrit dictates the efficiency of drug carriers to interact with inflamed endothelium in vitro. The presented data will suggest the optimum drug carrier size(s) and/or shape for vascular-targeted drug delivery applications in chronic inflammation and cardiovascular disease.